Inhaled Corticosteroids: Indications & Use

• Adrenal cortical hormones are steroids secreted by the adrenal cortex.
• Endogenous refers to substances produced inside the body.
• Exogenous refers to substances manufactured outside the body to be placed inside, such as medication.
• Immunoglobulin E (IgE) is a gamma globulin produced by respiratory tract cells.
• Prostaglandins are hormone-type substances circulating throughout the body.
• Steroid diabetes is hyperglycemia resulting from glucocorticoid therapy.
• Glucocorticoids break down proteins and fats to generate building blocks for gluconeogenesis.
• Steroids, also known as glucocorticoids or corticosteroids, produce an anti-inflammatory response.

Clinical Indications for Use of Inhaled Corticosteroids

• Inhaled corticosteroids are available for oral inhalation (lung delivery) and intranasal delivery.
• Orally inhaled agents: Used for maintenance and control therapy of chronic persistent asthma (step 2 care or greater).
• Step 2 asthma: Symptoms occur more than 2 days/week but not daily; night awakenings occur 3-4 nights/month; FEV1 or PEF is 80% of predicted or greater.
• Inhaled agents can be used with systemic corticosteroids in severe asthma.
• May allow reduction or elimination of systemic corticosteroids for asthma control.
• Inhaled corticosteroids in combination with other agents are recommended by the American Thoracic Society (ATS).

Identification of Aerosolized Corticosteroids

• Beclomethasone dipropionate HFA (QVAR) is an aerosolized corticosteroid.
• Flunisolide hemihydrate HFA (AeroSpan) is an aerosolized corticosteroid.
• Fluticasone propionate (Flovent HFA, Flovent Diskus) is an aerosolized corticosteroid.
• Fluticasone furoate (Arnuity Ellipta) is an aerosolized corticosteroid.

Identification of Aerosolized Corticosteroids (Combinations)

• Fluticasone propionate/salmeterol (Advair Diskus, Advair HFA) is a combination aerosolized corticosteroid.
• Budesonide/formoterol fumarate HFA (Symbicort) is a combination aerosolized corticosteroid.
• Mometasone furoate/formoterol fumarate HFA (Dulera) is a combination aerosolized corticosteroid.
• Fluticasone furoate/vilanterol (Breo Ellipta) is a combination aerosolized corticosteroid.

Hypothalamic–Pituitary–Adrenal Axis (HPA Axis)

• This is the pathway for release and control of endogenous corticosteroids.
• Stimulation of the hypothalamus causes release of corticotropin-releasing factor (CRF).
• CRF goes to the anterior pituitary gland where corticotropin is released into the bloodstream.
• Corticotropin, or adrenocorticotropic hormone (ACTH), stimulates the adrenal cortex to secrete glucocorticoids, such as cortisol.

HPA Suppression with Steroid Use

• The body cannot distinguish between endogenous and exogenous steroids.
• Administration of glucocorticoid drugs raises the body’s level
• Inhibits the hypothalamus and pituitary glands, causing HPA or adrenal suppression.

Physiology of Aerosolized Corticosteroids

• The production of the body’s own glucocorticoids follows a diurnal or circadian rhythm.
• Cortisol levels are highest in the morning at 8 a.m.
• Jet lag and night shift work can interfere with the cycle.

Alternate-day steroid therapy

• Alternate-day steroid therapy mimics the natural diurnal rhythm.
• The steroid drug is given early in the morning when normal tissue levels are high.
• On alternate days, regular diurnal secretion in the HPA system can resume.

Corticosteroids

• Corticosteroids are used with asthmatics and COPD patients to achieve an anti-inflammatory effect.

Nature of Inflammatory Response

• Inflammation produces redness, swelling, heat, and pain.
• Triple response: redness
• Local dilation of blood vessels, occurring in seconds.
• Triple response : flare
• Reddish color spreads several centimeters from the site, occurring 15 to 30 seconds after injury.
• Triple response: wheal
• Local swelling, occurring in minutes.

Nature of Inflammatory Response: Four Categories

• Increased vascular permeability causes an exudate to form in surrounding tissues.
• Leukocytic infiltration: White blood cells (WBC) emigrate through capillary walls (diapedesis) in response to attractant chemicals (chemotaxis).
• Phagocytosis: White cells and macrophages (in lungs) ingest and process foreign material such as bacteria.
• Mediator cascade: Histamine and chemoattractant factors are released at the injury site.
• Various inflammatory mediators, such as complement and arachidonic acid products, are generated.

Nature of Inflammatory Response

• Chronic bronchitis (usually caused by tobacco smoking) and asthma trigger airway inflamation.
• Treatment with anti-inflammatory agents such as glucocorticoids reduces basal level of airway inflammation.
• This reduces airway hyperresponsiveness and predisposition to acute episodes of obstruction.

Asthmatic reactions

• Asthmatic reactions are biphasic: early and late phase.
• Early asthmatic response is caused by immunoglobulin E (IgE).
• This early response peaks at ~15 minutes.
• Mast cells and eosinophils are the major cells responsible for an inflammatory response in asthma.
• Mast cell mediators and release of cytokines recruit other inflammatory cells to cause late-phase reaction.
• This late responsse occurs after ~6–8 hours and can last up to 24 hours.

Aerosolized Corticosteroids pg. 175 •Evidence of beneficial, complementary interaction between glucocorticoids and β-adrenergic agonists •Steroids increase β2-adrenergic receptor transcription •Inhaled corticosteroid therapy can provide partial protection against the development of tolerance •Salmeterol has been shown to promote binding of the glucocorticoid receptor to the response element of the cell’s nuclear DNA

•Mode of action •To induce gene expression for antiinflammatory proteins and receptors •To suppress gene expression for proinflammatory proteins •Mode of action (cont.) •Three general actions of suppression: 1.Upregulate transcription of antiinflammatory genes for substances, such as lipocortin 2.Suppress factors such as activator protein-1 (AP-1) and nuclear factor-κB (NF-κB), which cause transcription of genes involved in inflammation 3.Upregulate expression of inhibitors of NF-κB, such as inhibitor protein IκB •Effect on WBC count ➢Demargination: Depletion of neutrophil stores reduces their accumulation at inflammatory sites and in exudates ➢Overall increase in white cell count ➢Constriction of microvasculature to reduce leakage of cells and fluids into inflammatory sites •Effect on β-receptors •Restore responsiveness to β-adrenergic stimulation •Enhance β-receptor stimulation by increasing the number and availability of β-receptors on cell surfaces and by increasing the affinity of the receptor for β-agonists Steroid Use: Hazards and Side Effects •Systemic administration of steroids: •Suppression of the HPA axis •Immunosuppression •Psychiatric reactions •Dysphonia •Myopathy of striated skeletal muscle Cough •Fluid retention •Hypertension •Increased WBC count •Dermatological changes •Slowing of growth in children •Hyperglycemia •Systemic side effects with aerosol administration (of major concern): ➢HPA axis suppression ➢Growth restriction in children •Systemic side effects with aerosol administration (potential): •Adrenal insufficiency •Allergic inflammation after cessation •Suppression of HPA function •Growth reduction in children •Topical (local) side effects with aerosol administration: •Common: •Oropharyngeal candidiasis (oral thrush) (MOST COMMON) •Dysphonia •Cough •What to do: •Use minimal dose •Use spacer Clinical Application of Aerosol Steroids •Use in asthma ➢Early use in asthma ➢For acute severe asthma ➢Clinical use of inhaled corticosteroids •Use in COPD ➢Relieves symptoms ➢Little or no effect on FEV1 Respiratory Care Assessment of Inhaled Corticosteroid Therapy •Instruct patient in correct use of delivery system •Controller…not a rescue agent! •Respiratory rate and pattern •Breath sounds •Pulse •Subjective response •Use of peak flow meter •Exacerbations, missed work/school, ER visits •Assess for side effects

This lesson covers adrenal cortical hormones, steroids, and inhaled corticosteroids. It also discusses clinical indications for using inhaled corticosteroids for maintenance and control therapy of chronic persistent asthma.